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Dual-color imaging of nascent blood vessels vascularizing pancreatic cancer in an orthotopic model demonstrates antiangiogenesis efficacy of gemcitabine.

BACKGROUND: The stem cell marker nestin recently has been shown to be expressed in nascent blood vessels in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice. MATERIALS AND METHODS: In the present study, we visualized by dual-color fluorescence imaging tumor angiogenesis in the ND-GFP transgenic nude mice after orthotopic transplantation of the MIA PaCa-2 human pancreatic cancer line expressing red fluorescent protein. Mice were treated with gemcitabine at 150 mg/kg/dose on days 3, 6, 10, and 13 after tumor implantation. At day 14, mice were sacrificed and mean nascent blood vessel density and tumor volume were calculated and compared to control mice. RESULTS: Nestin was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that CD31 co-localized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. Gemcitabine significantly decreased the mean nascent blood vessel density in the tumor as well as decreased tumor volume. CONCLUSION: The dual-color model of the ND-GFP nude mouse orthotopically implanted with RFP-expressing pancreatic tumor cells enabled the simultaneous visualization and quantitation of tumor angiogenesis and tumor volume. These results demonstrated for the first time that gemcitabine is an inhibitor of angiogenesis as well as tumor growth in pancreatic cancer. The results have important implications for the clinical application of gemcitabine in this disease.

Angiogenesis Inhibitors↗

Role of container vessels in the introduction of exotic species.

Ballast water exchange practices were monitored on 28 incoming container vessels at the Port of Montreal. Measurements on 15 vessels indicated 13 of 32 tanks had salinities of <30 per thousand. The 16 transits with a North Atlantic route visited 31 of 37 ports located on freshwater or near freshwater outflows. Ballast carried by this vessel type represents an important means for the introduction of species on a global scale because of its transit routes, dockside discharge and moving ballast between tanks. Container vessels represent about 15% of the world fleet, but account for 32% of all visits to global ports, and 46% of visits to the 25 largest ports. The 10 ports that handled the largest volumes of international cargo also included 8 that handled the most cargo containers. Large ports can receive over 100,000 visits by all vessel types annually, and serve as hubs for over 500 ports in 100 countries. Secondary transport of exotic species is also a concern because of frequent visits by regional vessels.

Animals↗

Analysis of recent vessel arrivals and ballast water discharge in Alaska: toward assessing ship-mediated invasion risk.

Ships are a dominant vector for biological invasions through ballast water discharge (BWD) and hull fouling. Here, we provide a first comprehensive analysis of shipping in Alaska, summarizing (a) the number, type and origin of vessel arrivals to Alaska for 2003 and 2004, (b) the spatial and temporal variation in vessel traffic, and (c) the available data on ballast water discharge in order to prioritize locations for tracking biological invasions. Most arrivals were passenger vessels, followed by ferries and fishing vessels, all of which carried little ballast water. Regional and seasonal patterns in arrivals and BWD were unevenly distributed among vessel types. The majority of vessels reporting BWD were from foreign ports, and most of this ballast was untreated. The largest volumes of ballast were from tankers at Valdez and Kenai Peninsula ports. Although Alaska has few documented invasions, opportunities for ship-mediated transfer now appear high and warrant further scrutiny.

Alaska↗

Nitrosoglutathione improves blood perfusion and flap survival by suppressing iNOS but protecting eNOS expression in the flap vessels after ischemia/reperfusion injury.

BACKGROUND: The effects of nitric oxide (NO) on the microcirculation and free tissue survival remain controversial. With the use of a rat inferior epigastric artery flap as an ischemia/reperfusion injury (I/R) model, we investigated whether exogenous NO donation regulates endogenous NO synthase (NOS) expression in the flap vessels and promotes flap survival. METHODS: Thirty minutes before flap reperfusion, normal saline (1 ml), nitrosoglutathione (GSNO 0.2, 0.6, 3 mg/kg), or N(G)-nitro-L-arginine-methyl ester (L-NAME, 450 mg/kg), was injected intravenously into 20 rats. Total plasma NOx (NO(2)-/NO(3)-) was measured to reflect NO production. Immunohistochemical staining was investigated for the endothelin-1 (ET-1) and NOS isoforms expression on the flap vessels. NOS isoforms expression was evaluated by Western blot. Laser-Doppler flowmetry monitored flap perfusion. Survival areas were assessed by gross examination at 7 days postoperatively. RESULTS: Flap ischemia at 12 hours followed by reperfusion resulted in endothelial cell damage, as demonstrated by induction of iNOS and ET-1 expression in the flap vessels. An optimal dose of nitrosoglutathione (0.6 mg GSNO/kg) significantly increased plasma NOx levels (P=.027) and improved flap perfusion by laser Doppler measurement (P=.014), and increased the flap viability area (P<.001). Additionally, it selectively suppressed iNOS induction, but enhanced eNOS expression and decreased ET-1 deposition in the flap vessels. In contrast, an NOS inhibitor, N(G)-nitro-L-arginine methyl ester, inhibited both iNOS and eNOS expression in the flap vessels, decreased endogenous NOx production, and compromised flap viability. CONCLUSION: This study indicates that intravenous administration of exogenous GSNO can appropriately donate NO to suppress iNOS induction and enhance eNOS expression in pedicle vessels, resulting in better blood perfusion and a higher flap survival after I/R injury.

Animals↗

Imaging of pancreatic transplant vessels and anastomoses with 16-row multidetector computed tomography.

The aim of this study was to evaluate the usefulness of 16-row multidetector computed tomography (16-MDCT) in the assessment of the potency of arterial and venous vessels in combined kidney-pancreas transplant and detection of transplant-related complications. Fifteen patients underwent a combined kidney-pancreatic transplantation. On the seventh day after the operation, we performed 16-MDCT in arterial and portal venous phase to evaluate vessels, anastomotic sites, and pancreatic parenchymal vascularization as well as peripancreatic fluid collections. We visualized the pancreatic vessels and anastomosis sites in all cases. In 12 recipients, there were no abnormal findings as regards the patency of the arterial and venous vessels and the vascularization of the pancreatic parenchyma. In two patients, complete arterial thrombosis of the body and tail pancreatic graft vessels was recognized at 2 weeks after transplantation, resulting in graft removal. Thrombi were localized in the distal part of anastomoses. None of the patients had venous thrombosis. One recipient had stenosis of the venous anastomosis. Peripancreatic fluid collections were observed in seven patients. In conclusion, 16-MDCT is an efficient method to estimate pancreatic transplant vessels, localize thrombi, and detect other transplant-related complications.

Anastomosis, Surgical↗

Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos.

Blood vessel development is in part regulated by pericytes/presumptive vascular smooth muscle cells (PC/pvSMCs). Here, we demonstrate that interactions between PC/pvSMCs and extracellular matrix play a critical role in this event. We show that the cranial vessels in alpha4 integrin-deficient mouse embryos at the stage of vessel remodeling are increased in diameter. This defect is accompanied by a failure of PC/pvSMCs, which normally express alpha4beta1 integrin, to spread uniformly along the vessels. We also find that fibronectin but not VCAM-1 is localized in the cranial vessels at this stage. Furthermore, cultured alpha4 integrin-null PC/pvSMCs plated on fibronectin display a delay in initiating migration, a reduction in migration speed, and a decrease in directional persistence in response to a polarized force of shear flow. These results suggest that specific motile activities of PC/pvSMCs regulated by mechanical signals imposed by the interstitial extracellular matrix may also be required in vivo for the distribution and function of the PC/pvSMCs during blood vessel development.

Animals↗

Abrupt vessel closure: changing importance, management, and consequences.

Percutaneous coronary interventions have been performed for 20 years. Despite the success and progress of these interventions, abrupt vessel closure has been a dramatic adverse event of coronary interventions. Closure has frequently led to the major complications of death, myocardial infarction, and emergency coronary artery bypass. Because of the fear of this adverse event and its subsequent complications, the applicability of coronary interventions is sometimes limited. The pathologic characteristics of abrupt vessel closure have been recognized as predominantly caused by dissection, with vessel recoil and thrombus formation playing important secondary roles. The recognition of the lesions at risk for abrupt vessel closure has led to a strategy of lesion-specific device therapy to reduce complications. Similarly the role of antiplatelet and antithrombotic therapies have reduced complications. The earliest methods of dealing with abrupt closure was emergency coronary artery bypass surgery with significant rates of morbidity and mortality. With the advent of second-generation devices and techniques, particularly stents, the management of abrupt vessel closure has been simplified and alternatives to emergency coronary bypass are more available. This article will review the history and current status of the prevention and management of abrupt vessel closure and demonstrate that anticipation and management of this complication have been facilitated with reduction of subsequent complications and increased applicability of coronary interventions.

Angioplasty, Balloon↗

Umbilical and placental vessels: modifications of their mechanical properties in preeclampsia.

OBJECTIVES: Our objective in this study was to assess the basic mechanical properties of umbilical and chorionic vessels of placentas delivered after both normal and preeclamptic pregnancies. STUDY DESIGN: Placentas were selected when the parturient women were admitted to the delivery room. Normal pregnancy (n = 17) was characterized by delivery at term (38 to 40 weeks) after uncomplicated pregnancy without any medication. Preeclamptic pregnancy (n = 7) was characterized by delivery after 28 weeks of pregnancy (28 to 39 weeks) after sustained hypertension and proteinuria. Arteries and veins from the umbilical cord and chorionic plate were prepared in rings for in vitro study in tissue baths. Passive and active (on stimulation by potassium chloride or serotonin) mechanical properties of these vessels were studied. RESULTS: In vessels from normal pregnancy, responsiveness, but not sensitivity, was increased with increasing passive tension on vessels until optimal tension was reached. The passive stretch-tension curve was shifted downward in umbilical veins and upward in umbilical arteries and chorionic veins obtained from preeclamptic mothers in comparison with normal parturient women. In the absence of passive tension, contractions in response to potassium chloride were produced in all umbilical veins and some chorionic veins from preeclampsia but not from normal pregnancy. Developed wall tension curves in chorionic vessels from preeclampsia were shifted upward. In umbilical veins and arteries and in chorionic veins, the optimal passive tension was lower in tissues from preeclampsia than in tissues from normal pregnancy. CONCLUSION: Our results indicate that both passive and active mechanical properties of umbilical vessels are modified after pregnancy complicated by preeclampsia.

Arteries↗

Free flaps and irradiated recipient vessels: an experimental study in rabbits.

In an experimental study in rabbits the effect of previous irradiation to the recipient vessels on the survival rate of free flaps was evaluated. Pre-operative radiotherapy was given in a single anterior neck field using a Cobalt60 unit, 1.25 MeV, SSD 80 cm in a fractionated dose corresponding to 5000 rad/5 weeks. An experimental model using paired data was established using two epigastric free flaps in each animal: one anastomosed to the irradiated vessels (carotid and jugular vein) and implanted outside the irradiated field and the other flap anastomosed to the normal femoral vessels and also implanted outside the irradiated field. In a sequential analysis it was found that free flaps anastomosed to irradiated recipient vessels within 12 weeks from the start of radiotherapy failed significantly more often than free flaps anastomosed to normal recipient vessels (p less than 0.10). This supports the view that preference should be given to the use of non-irradiated recipient vessels for microvascular transfer of free flaps.

Animals↗

Visualization of the epigastric vessels and bladder before laparoscopic trocar placement.

OBJECTIVE: Transillumination and laparoscopic visualization are two techniques recommended to minimize the risks of injury to abdominal wall structures during insertion of secondary trocars. This study was designed to determine the effectiveness of these techniques to locate the epigastric vessels and superior bladder margin. DESIGN: Prospective observational. SETTING: Academic medical centers. PATIENT(S): One hundred five women undergoing laparoscopy for tubal sterilization, infertility, pelvic masses, or pelvic pain. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The ability to visualize the superficial and inferior epigastric vessels, and bladder margin; body mass index (BMI; in kilograms per meter squared); and skin color. RESULT(S): Transillumination successfully visualized 64% of superficial epigastric vessels and was less effective both as weight increased (BMI <25 kg/m(2): 86%; BMI = 25-30 kg/m(2): 61%; BMI >30 kg/m(2): 25%) and in dark-skinned women (69%) compared to those with lighter skin (42%). Laparoscopic visualization successfully identified 82% of inferior epigastric vessels and 46% of bladder margins, and was less effective as weight increased. CONCLUSION(S): Transillumination can successfully locate superficial epigastric vessels, and laparoscopic visualization can locate inferior epigastric vessels and the superior bladder margin in the majority of women undergoing laparoscopy. Transillumination is less effective in dark-skinned women, and both techniques are less effective with increasing body weight.

Body Weight↗

Critical evaluation of a pressure-sensitive capsule for measurement of esophageal varix pressure. Studies in vitro and in canine mesenteric vessels.

The accuracy and reliability of a noninvasive pressure-sensitive capsule for the endoscopic measurement of esophageal varix pressure was evaluated. Capsule pressure was correlated with direct intraluminal pressure measurements. The influence of vessel wall tension on capsule pressure was also assessed. In vitro studies demonstrated an excellent correlation (r greater than or equal to 0.94; p less than 0.001) between the pressure obtained with the capsule and intraluminal pressure over a range of vessel diameters and wall thicknesses. In vivo correlation of pressures obtained with the capsule with direct venous pressure measurements was excellent (r = 0.85). However, this correlation decreased with a decrease in vessel diameter (group 1 diameter greater than or equal to 10 mm, r = 0.95; group 2 diameter greater than or equal to 5 mm but less than 10 mm, r = 0.75; group 3 diameter greater than or equal to 3 mm but less than 5 mm, r = 0.81). This decrease in accuracy was significant (p less than 0.001) between group 1 and groups 2 and 3. In vitro and in vivo, capsule pressure variability was significantly greater (p less than 0.001) in vessels of smaller diameter. Wall tension significantly influenced capsule pressure (p less than 0.05), although this effect was only seen in large "vessels" with a diameter beyond a clinically relevant range. Therefore, despite obtaining technically acceptable capsule pressure measurements in ideal experimental conditions, the accuracy and variability of these measurements are limited by vessel size.

Animals↗

Effect of the NO scavenger carboxy-ptio on endothelium-dependent vasorelaxation of various blood vessels from rabbits.

In the present study, we investigated the effect of a nitric oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide [carboxy-PTIO], on endothelium-dependent relaxation of a series of blood vessels from rabbits, such as thoracic aorta and femoral, renal, mesenteric, and pulmonary arteries, using a functional muscle bath technique. Carboxy-PTIO produced concentration-dependent contractions in various vessels. The contractile responses in renal, mesenteric, and pulmonary arteries were significantly greater than those in the aorta and femoral artery. Similarly, phenylephrine-induced contractions in renal, mesenteric, and pulmonary arteries were markedly enhanced after pretreatment with carboxy-PTIO. Also, carboxy-PTIO inhibited acetylcholine-induced relaxation in various blood vessels. The maximum inhibitions in aorta and femoral artery were significantly greater than those in renal, mesenteric, and pulmonary arteries. The present data demonstrate that carboxy-PTIO reduces basal, phenylephrine-, and acetylcholine-induced release of NO in rabbit blood vessels. However, different degrees of inhibition of endothelium-dependent vasorelaxation were observed in various vessels. Specifically, the thoracic aorta and femoral artery are less susceptible to the action of carboxy-PTIO without acetylcholine than renal, mesenteric, and pulmonary arteries. Conversely, the most potent carboxy-PTIO-induced inhibition of acetylcholine-induced vasorelaxation was observed with aorta and femoral arteries. Thus, it is suggested that the contribution of endogenous NO to vascular tone and regional blood flow may vary among different rabbit blood vessels.

Acetylcholine↗

Randomized trial of suture versus electrosurgical bipolar vessel sealing in vaginal hysterectomy.

OBJECTIVE: To compare blood loss and procedure time of vaginal hysterectomy using an electrosurgical bipolar vessel sealer versus using sutures. METHODS: Sixty patients scheduled for vaginal hysterectomy in a single surgical practice were randomized to either electrosurgical bipolar vessel sealer or sutures as the hemostasis technique. Procedure time was defined as time from initial mucosal injection to closure of the vaginal cuff with satisfactory hemostasis. Blood loss was estimated by the anesthesia service. Statistical methodology included the Student t and Wilcoxon rank-sum tests, and all comparisons were two tailed, with P <.05 considered significant. RESULTS: Use of an electrosurgical bipolar vessel sealer resulted in shorter procedure times: The mean procedure time in the electrosurgical bipolar vessel sealer arm was 39.1 minutes (range 22-93) versus 53.6 minutes (range 37-160) for the suture arm (P =.003). Mean estimated blood loss was also statistically less with electrosurgical bipolar vessel sealer: 68.9 mL (range 20-200) versus 126.7 mL (range 25-600) for the suture arm (P =.005). Complication rate and length of stay did not differ by hemostasis technique. Seventy-eight percent of all cases were outpatient. CONCLUSION: Electrosurgical bipolar vessel sealer is an effective alternative to sutures in vaginal hysterectomy, resulting in significantly reduced operative time and blood loss.

Adult↗

Progression of lymphatic vessel dilatation in the presence of living adult Wuchereria bancrofti.

Bancroftian filariasis, a mosquito-transmitted disease commonly known as elephantiasis, is caused by infection with the parasite Wuchereria bancrofti. Infection with this parasite can induce a broad array of chronic debilitating and socially stigmatizing conditions, but the pathogenesis of this morbidity remains obscure. Recent evidence indicates that in filariasis-endemic areas the primary lesion is not lymphatic vessel obstruction but, rather, dilatation. To determine the extent to which lymphatic dilatation occurs in the presence of living adult W. bancrofti, we performed longitudinal ultrasonographic measurements in 80 men (mean age 24 years) in Brazil who had a total of 107 W. bancrofti nests detectable by ultrasound. Initial mean lymphatic vessel diameter at the site of the worms was 3.4 mm (range, 0.7-11.3), and was greater in men with 2 or more nests (3.9 mm) than in those with only one nest (3.0 mm, P = 0.003). During the study period (2-35 months, mean, 13.7), lymphatic vessel diameter increased at the site of 92 (86.0%) adult worm nests. Mean rate of increase of lymphatic vessel diameter was 1.2 mm per person-year (range, 0-0.93 mm per month). In a general linear model, no factors, including treatment with antifilarial drugs, were significantly associated with rate of vessel diameter increase. Thus, lymphatic vessel dilatation progress in the presence of living adult W. bancrofti; the rate of this progression is heterogeneous. These data suggest that lymphatic dilatation will continue to progress in most infected persons even after mass treatment with currently recommended antifilarial drugs. In addition to interrupting transmission, the global programme for elimination of lymphatic filariasis should address the potential for disease progression in persons who remain infected with adult W. bancrofti.

Adolescent↗

Preservation of the anterior ciliary vessels during extraocular muscle surgery.

Conventional, full-tendon, rectus muscle surgery disrupts the anterior ciliary vessels. This may lead to anterior segment ischemia when the number of interrupted vessels is sufficient to significantly compromise anterior segment blood flow. Clinical observations and histologic studies provide new anatomic information concerning the course of the anterior ciliary vessels in the sub-Tenon's region. These studies demonstrate the feasibility of dissection and preservation of the anterior ciliary vessels during rectus muscle surgery. Dissection and preservation of 35 clinically apparent anterior ciliary vessel groups were attempted on 15 rectus muscles during strabismus surgery. The unplanned vessel destruction rate was 9.5%. Procedures included 12 recessions, 1 resection, and 2 full-tendon transpositions. The possible role of this procedure in the prevention of anterior segment ischemia is discussed.

Adolescent↗

Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies.

The purpose of this study was to explore the sequential imaging and histologic alterations of tumor blood vessels in the patient with solid malignancies after extracorporeal treatment of high-intensity focused ultrasound (HIFU). A total of 164 patients underwent extracorporeal HIFU ablation of malignant solid tumors. After HIFU treatment, enhanced magnetic resonance imaging (MRI), color Doppler ultrasound (US) imaging, dynamic radionuclide scanning, digital subtraction angiography, and histologic study were performed to monitor the response of tumor vessels to HIFU ablation. Compared with tumor images in the patients before HIFU, clinical images showed an abrupt interruption, followed by the cessation of blood flow within the tumor vessels after HIFU treatment. The histologic examination indicated that not only the treated tumor cells showed coagulative necrosis, but also small tumor vessels were severely damaged by the HIFU treatment. The results strongly imply that the damaged tumor vessels might play a critical role in secondary tumor cell death, and then indirectly strengthen the destructive force of focused US beams on tumor tissue. It is concluded that tumor vessel damage can be induced by HIFU, which may be a promising strategy in the treatment of patients with solid malignancies.

Adolescent↗

Tumour vessel damage resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy.

This study examined tumour vessel injury resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy (PDT) in the treatment of rat liver tumours by means of scanning electron microscopy. A total of 18 Wistar rats were divided into three groups. Group I (six animals) underwent hyperthermia for 15 min (15-min hyperthermia). Group II (six animals) underwent hyperthermia for 30 min (30-min hyperthermia). Group III (six animals) received the combined treatment of PDT and 30-min hyperthermia. For PDT, delta-amino laevulinic acid at a dose of 60 mg/kg of body weight was intravenously administered 60 min before irradiation at 635 nm. The morphological results indicated that 15-min hyperthermia gave rise to an increase in permeability of the vessels in the treated tumour. Thirty-min hyperthermia caused extreme oedema of vascular endothelial cells and restrictive openings of tumour branch vessels. The combined therapy of PDT and hyperthermia destroyed tumour vasculature. Large breaks of the inner wall of the treated tumour vessels were deeply involved in the basement membrane of the vessel. The results indicate that there may be a close link between inhibition of tumour growth and degree of damage to tumour vessels.

Animals↗

Multiparameter fluorescence mapping of nonprotein sulfhydryl status in relation to blood vessels and hypoxia in cervical carcinoma xenografts.

PURPOSE: Aberrant architecture of the tumor vasculature and temporal fluctuations in blood flow can result in tumor hypoxia. The aim of this study was to classify tumor hypoxia based on distance to blood vessels, and to characterize its biologic significance by determining levels of nonprotein sulfhydryls (NPSH) in hypoxic regions located proximally and distally to tumor blood vessels. METHODS AND MATERIALS: A dual fluorescence method was developed for the spatial colocalization of the vasculature and hypoxia in frozen sections from SiHa cervical carcinoma xenografts. A parallel section was stained with the sulfhydryl stain mercury orange. Composite fluorescence images were generated by imaging and tiling individual fields of view into 2D image arrays. Image arithmetic techniques were combined with feature-based image segmentation to characterize expression of NPSH as a function of the hypoxic tumor microenvironment. RESULTS: NPSH levels were higher in hypoxic areas of the SiHa xenografts (15.1 +/- 0.5 vs. 13.5 +/- 0.5 integrated optical density [IOD], p < 0.03). When tumor hypoxia was classified by distance to the nearest visible blood vessel, significantly higher NPSH levels were found in hypoxic regions close to blood vessels than in regions at a distance from blood vessels. CONCLUSION: The results of this study indicate differential expression of NPSH levels in regions of hypoxia that are proximal or distal to blood vessels in SiHa tumors.

Animals↗